Fig. 3: Cell invasion into adipose tissues is MMP-independent.

a Schematic representation of norbornene-functionalised hyaluronic acid (NB-HA)-based organohydrogels (OHGs) presenting matrix metalloproteinase (MMP)-degradable crosslinking peptides and cell adhesion ligands. b Storage moduli of collagen- and NB-HA-based OHGs (n = 5 collagen-based and n = 3 NB-HA-based OHGs; average ± s.e.m.). c Normalised stress-relaxation curves of collagen- and HA-NB OHG (n = 5 collagen-based and n = 3 NB-HA-based OHGs). d F-actin (grey) and nuclei (red) in OVCAR8 cells embedded in collagen- or NB-HA-based OHGs for 7 d (representative images from n = 9 spheroids). e OVCAR8 spheroid area in collagen- or NB-HA-based OHGs relative to collagen-based OHG average (n = 9 spheroids). f F-actin (grey) and nuclei (red) of OVCAR8 cells embedded in GFOGER- or RGD-presenting NB-HA OHG (representative images from n = 9 spheroids). g BODIPY (green), nuclei (red), and F-actin (grey) of OVCAR8 in GFOGER- or RGD-presenting NB-HA OHG (representative images from n = 9 spheroids). Arrowheads indicate cells in direct contact with oil microdroplets. h OVCAR8 spheroid area in GFOGER- or RGD-presenting NB-HA OHG after 7 d culture relative to GFOGER OHG average (n = 9 spheroids). i F-actin (grey) and nuclei (red) in OVCAR8 cells embedded in collagen-based OHGs for 7 d (representative images from n = 8 spheroids). j OVCAR8 spheroid area in collagen-based OHGs after 7 d culture relative to DMSO control (n = 8 spheroids). k BODIPY (green) and mRFP (red) staining of peritoneal adipose tissue explants and mRFP-OVCAR8 cells. l Quantification of mRFP-OVCAR8 organotypic invasion depth into human peritoneal tissues after 7 d (n = 3 tissues from distinct donors). Rhombuses indicate the average. m OVCAR8 spheroid area quantifications in MMP-cleavable or non-cleavable NB-HA OHG after 7 d culture relative to MMP-cleavable control (n = 11 spheroids). For the data in (b, e, h, j and l), a two-sided unpaired t test was performed. One-way analysis of variance (ANOVA) with Tukey’s correction for multiple comparisons was performed for the data in (m). Error bars in (b) represent the s.e.m. Scale bars, 100 μm (g, k), 200 μm (d, f, i). Source data are provided as a Source Data file.